Blood flow reductions in the heart can result in dysfunction of this organ and cell death if the flow reduction is severe enough. Restoration of coronary blood flow early during a heart attack is becoming a clinical reality with the advent and improvements in thrombolytic, mechanical, and surgical interventions. While early restoration of blood flow, for example, by thrombolysis or following transient ischemia, can prevent or mitigate the degree of cell death (infarction) occurring, reperfusion can still result in some degree of cardiac dysfunction or cell death (also referred to as stunned myocardia). Thus, it would be of great clinical value to find a means to preserve reperfusion function of the heart.
Thromboxane A.sub.2 (TXA) which is released from the heart during reperfusion is thought to have physiological effects that may adversely influence myocardial performance, namely, TXA contributes to post ischemic contractile dysfunction, Hoeft, A., et al., "Preservation of myocardium in transient ischemia by the thromboxane synthetase inhibitor." UK-38,485. Res. Exp. Med. 1986; 186:35-46, and Schror, K., et al."Treatment of acute myocardial ischemia with a selective antagonist of thromboxane receptors. (BM 13,177)" Br. J. Pharmacol. 1986; 87:631-7.
Hoeft et al, supra, and Schror et al, supra, demonstrate the ability of TXA inhibitors or antagonists to reduce the severity of ischemia in some experimental models, though the physiological mechanisms of action of these compounds on post-ischemic recovery of function are still unknown. For instance, it is thought that TXA is released during ischemia as well as during reperfusion and thus TXA antagonists may be working during coronary occlusion Schmitz, J. M., et al., "Vascular prostaglandin and thromboxane production in a canine model of myocardial ischemia." Circ. Res. 1985 57:223-31, Michael, L. H., et al., "Myocardial ischemia: platelet and thromboxane concentrations in cardiac lymph and the effects of ibuprofen and prostacyclin." Circ. Res. 1986; 59:49-55.